Automobile driving is a crucial aspect of everyday life, yet vehicular crashes pose a serious public health problem. Drivers with Parkinson's disease (PD) are at special risk for a crash due to progressive impairments of motor function, cognition, and daytime arousal. Some drivers with PD are especially likely to drive while impaired because they are not aware of performance impairments, and neither are their physicians. Judgments on fitness to drive in at-risk drivers with PD should rely upon empirical observations of performance, because decisions based on medical diagnosis or age alone may unfairly deny patients their mobility or unwisely authorize licensure in unfit drivers. We propose to expand the available knowledge of driving safety in PD by testing a set of hypotheses in experiments that will assess (1) motor function using standardized measures of parkinsonism, (2) cognitive functions using standardized neuropsychological tests (of attention, perception, memory, and executive functions), (3) daytime arousal (standard self-ratings of sleepiness and monitoring of lid closure), and (4) driving performance as measured in an instrumented vehicle and a state-of-the-art interactive driving simulator. Our pilot study of drivers with PD shows the feasibility of this approach. Simulators make it possible to observe driver errors with optimal stimulus and response control in an environment that is challenging yet safe for the driver and tester. Participants in this project will be 115 legally licensed drivers with PD and an equal number of control drivers without neurological disease. Allowing for attrition, 100 of these 115 drivers with PD will be re-tested two years after the initial driving assessment to measure effects of PD progression on driver safety. Our goal is to increase understanding of the role of PD-related motor dysfunction, cognitive impairment, and daytime arousal disorders in driving safety errors. A better understanding of how driving performance deteriorates in PD and whether drivers are even aware of their impairment is a necessary step in the rational development of interventions that could help prevent crashes by patients with PD. The techniques used in this study could ultimately be adapted to develop future tools for screening, identifying, advising, and alerting drivers with PD who are at greater risk for impaired driving. Fair and accurate means of detecting unfit drivers with PD will help mitigate the tragedy of motor vehicle crashes caused by these impaired individuals.